Factors that regulate the growth and differentiation of erythroid cells are investigated in murine erythroid cells isolated at different phases of maturation by methods of cell separation. Cells are then permitted to differentiate and proliferate during short-term culture in the presence or absence of erythropoietin. The following aspects of erythroid cell maturation are being studied: synthesis of heme and hemoglobin, production of globin mRNA, development of membrane proteins, and abnormalities in these processes encountered in hematologic disorders in mouse and man. Studies of factors that regulate granulocyte proliferation are based on techniques of cell culture including the Millipore diffusion chamber method and colony assays of hemopoietic precursor cells. Attention is being focused on processes that may modulate the proliferative activity of granulocyte precursors, including cell-cell interactions and microenviornmental factors. Studies will be performed with regard to both normal granulocytopoiesis and abnormalities encountered in hematologic disorders in experimental animals and man. The renal erythropoietic factor (REF) is being investigated with the use of methods of protein purification in order to define the chemical nature of this material and also to prepare a radioimmunoassay to be used in physiological studies of the role of REF in erythropoiesis in vivo. Additional studies of REF and erythropoietin production are being peformed with the use of the isolated perfused rat kidney.